Immunotherapy is at an inflection point. After three decades of accelerating progress, immunotherapy is entering the realm of in vivo engineering. This Comment discusses the potential of in vivo engineering in addressing challenges met by ex vivo engineering efforts. Per a recent workshop organized by the National Institutes of Health, we highlight progress, the platform technologies fueling it, and elements of a road map and challenges ahead.
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Acknowledgements
We are grateful to Zhang-Zhi Hu, Connie Sommers and Marc Ernstoff at the National Cancer Institute / National Institutes of Health for organizing this workshop “In Vivo Engineering of Immune Cells (IVEIC) for Cancer Immunotherapy” (https://dctd.cancer.gov/about/news-events/events/past-events/iveic-cancer-immunotherapy) and for comments on the manuscript.
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A.B. conceived the structure of the article. A.B., S.G. and M.T.S. built and reviewed the article.
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A.B. is a consultant for AbbVie Inc, Cartesian Therapeutics, Elicio Therapeutics and A2 Biotherapeutics. M.T.S. is co-founder of and has received stock options from Persistence Therapeutics (Jupiter Bioventures) and has intellectual property licensing with Sanofi, Juno Therapeutics (now Bristol Myers Squibb) and Jupiter Bioventures. S.G. is a named inventor on multiple patents related to CAR-T cells, including in vivo transduction, that have been filed by the University of Pennsylvania, and he has received research funding from Novartis Pharmaceuticals. He is a consultant for AvenCell, Curris, Ship of Theseus, Cassidy Bio and Yellowstone.
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Bot, A., Stephan, M.T. & Gill, S. The dawn of in vivo immune cell engineering in oncology. Nat Biotechnol (2026). https://doi.org/10.1038/s41587-025-02979-0
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DOI: https://doi.org/10.1038/s41587-025-02979-0
